Interferon (IFN)-beta treatment enhances CD95 and interleukin 10 expression but reduces interferon-gamma producing T cells in MS patients

J Neuroimmunol. 1999 Apr 1;96(1):92-100. doi: 10.1016/s0165-5728(98)00271-9.


Interferon (IFN)-beta has been shown to favorably alter the disease course of relapsing-remitting multiple sclerosis (RRMS) patients. Although its mode of action is still unclear, there is ample evidence from in vitro studies that IFN-beta directly modulates the function of immune cells. We analyzed here the effects of IFN-beta treatment on immune functions in vivo in a group of 25 RRMS patients who received IFN-beta (8 MIU) on alternate days. At baseline and at 1, 3 and 6 months from the start of the treatment, parameters for differentiation and activation states of both monocytes and T lymphocytes were assessed. A transient increase was seen in plasma (p) interleukin (IL)-10 level whereas pIL-12 (p40) was not affected. A similar change was found in the ability of monocytes to secrete these cytokines in vitro. Notably, patients who in vitro readily responded to IFN-beta with enhanced IL-10 production had the highest pIL-10 levels. Concerning T-cell differentiation, flow cytometric analysis of cytokine production showed that treatment with IFN-beta moderately decreased the mean percentages of CD8pos T cells producing IL-2 and IFN-gamma and CD8neg T cells producing IL-4 (p<0.05 for all cytokines), whereas a more significant decline was seen in the mean percentage of CD8neg T cells producing IFN-gamma (p<0.01). This resulted in a significant lower ratio T(HELPER(H))1 vs. T(HELPER(H))2 type cells in the CD8pos T-cell subset (p<0.05), but not in the CD8neg T-cell subset. Finally, IFN-beta treatment resulted in an initial rise in the mean percentage of CD95pos T cells and in a gradual increase in the mean level of soluble CD95 (sCD95) in plasma (p<0.01). Additional in vitro studies showed that IFN-beta indeed rapidly (within 24 h) upregulates CD95 expression on both primed and unprimed T cells and augments the release of sCD95 in culture supernatants. Thus, we confirm here that IFN-beta treatment leads to similar changes in cytokine production of T cells and monocytes as previously described in vitro. Enhanced IL-10 secretion may downmodulate cytokine secretion by activated T cells and in this way dampen newly-induced and/or ongoing immune responses. In addition, we identified a novel effect of IFN-beta treatment, i.e., induction of CD95 expression. The augmentation of CD95 expression may directly interfere with T-cell selection, notably of autoaggressive T cells. Future studies are needed to show whether this increased CD95 expression indeed leads to increased apoptosis of immune cells.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adult
  • Antibodies, Monoclonal
  • Antigens, CD / analysis
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-beta / administration & dosage*
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / blood*
  • Interleukin-10 / metabolism
  • Interleukin-12 / blood
  • Interleukin-2 / blood
  • Interleukin-4 / blood
  • Lectins, C-Type
  • Male
  • Monocytes / chemistry
  • Monocytes / metabolism
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / therapy
  • Recombinant Proteins / administration & dosage
  • Solubility
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / metabolism*
  • fas Receptor / analysis
  • fas Receptor / blood*


  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Interleukin-2
  • Lectins, C-Type
  • Recombinant Proteins
  • fas Receptor
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Interferon-beta
  • Interferon-gamma